Department of Cardiology, University of Tartu, 8 Puusepa Street, Tartu, 51014, Estonia.
Cardiovasc Diabetol. 2012 Jul 13;11:58. doi: 10.1186/1475-2840-11-58.
Diabetes mellitus is associated with micro- and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation.
Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis.
PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH)D (493 ± 125 nmol/L vs 108 ± 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation.
PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media.
糖尿病与微血管和大血管并发症以及心血管风险增加有关。血清不对称二甲基精氨酸(ADMA)水平升高可能与糖尿病引起的血管损伤相关的内皮功能障碍有关。维生素 D 可能对动脉僵硬具有潜在的保护作用。本研究旨在研究糖尿病对主动脉的功能/结构特性以及内皮功能的影响,以及维生素 D 补充的影响。
雄性 Wistar 大鼠(n = 30)被随机分为对照组、未治疗的糖尿病组和糖尿病+胆钙化醇组。糖尿病通过腹腔注射链脲佐菌素诱导,随后在治疗组中口服胆钙化醇(500 IU/kg)10 周。使用双压力传感器导管在平均动脉压(MAP)范围为 50 至 200 mmHg 时记录主动脉脉搏波速度(PWV)。静脉内输注苯肾上腺素和硝酸甘油分别用于增加和降低 MAP。使用放射免疫测定法测量血清 25-羟维生素 D [25(OH)D]水平。通过酶联免疫吸附测定法测量血清 ADMA 水平。收集主动脉样本进行组织形态计量学分析。
MAP 高达 170 mmHg 时,各组之间的 PWV 没有明显差异,但在糖尿病大鼠中,MAP 为 170 至 200 mmHg 之间的 PWV 显著升高。尽管血清 25(OH)D 水平存在显著差异(分别为 493 ± 125 nmol/L 和 108 ± 38 nmol/L),但治疗组和未治疗的糖尿病组之间的等压 PWV 相似。与对照组相比,治疗组和未治疗的糖尿病组的血清 ADMA 水平均升高。未经治疗的糖尿病大鼠主动脉中层弹性层的浓度和完整性受损,维生素 D 补充可改善这一情况。
在等压条件下确定的 PWV 谱显示出未控制的糖尿病对主动脉僵硬度的不同影响。糖尿病还与血清 ADMA 水平升高有关。维生素 D 补充并未改善主动脉僵硬度或内皮功能的功能指标,但可防止主动脉中层弹性纤维的碎片化。